Novel heparan sulphate analogues:: inhibition of β-secretase cleavage of amyloid precursor protein

The role of HS (heparan sulphate) in the pathology of AD (Alzheimer's disease) is multifaceted. HS and other glycosaminoglycans have been widely reported to be associated with neuritic plaques. HS has also been shown to promote the aggregation of A beta (amyloid beta-peptide), the proteinaceous component of neuritic plaques. Recently, we described a novel and contrasting role for HS in the pathology of A beta: HS can inhibit the formation of AD, by directly interacting with the protease BACE1 (beta-site amyloid precursor protein cleaving enzyme 1; beta-secretase 1), that cleaves the amyloid precursor protein and is the rate limiting step in the generation of A beta. Here, we review the current roles of HS and the potential for HS-derivatives in the treatment of AD.